Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Academic Article uri icon

start page

  • 5312

end page

  • 5321

abstract

  • Gene expression profiling of 207 uniformly treated children with high-risk B-progenitor acute lymphoblastic leukemia revealed 29 of 207 cases (14%) with markedly elevated expression of CRLF2 (cytokine receptor-like factor 2). Each of the 29 cases harbored a genomic rearrangement of CRLF2: 18 of 29 (62%) had a translocation of the immunoglobulin heavy chain gene IGH@ on 14q32 to CRLF2 in the pseudoautosomal region 1 of Xp22.3/Yp11.3, whereas 10 (34%) cases had a 320-kb interstitial deletion centromeric of CRLF2, resulting in a P2RY8-CRLF2 fusion. One case had both IGH@-CRLF2 and P2RY8-CRLF2, and another had a novel CRLF2 rearrangement. Only 2 of 29 cases were Down syndrome. CRLF2 rearrangements were significantly associated with activating mutations of JAK1 or JAK2, deletion or mutation of IKZF1, and Hispanic/Latino ethnicity (Fisher exact test, P < .001 for each). Within this cohort, patients with CRLF2 rearrangements had extremely poor treatment outcomes compared with those without CRLF2 rearrangements (35.3% vs 71.3% relapse-free survival at 4 years; P < .001). Together, these observations suggest that activation of CRLF2 expression, mutation of JAK kinases, and alterations of IKZF1 cooperate to promote B-cell leukemogenesis and identify these pathways as important therapeutic targets in this disease.

date/time value

  • 2010

Digital Object Identifier (DOI)

  • 10.1182/blood-2009-09-245944

PubMed Identifier

  • 20139093

volume

  • 115

number

  • 26

keywords

  • Adolescent
  • Child
  • Cohort Studies
  • Female
  • Gene Expression Regulation, Leukemic
  • Hispanic Americans
  • Humans
  • Ikaros Transcription Factor
  • Janus Kinase 1
  • Janus Kinase 2
  • Janus Kinases
  • Kaplan-Meier Estimate
  • Male
  • Mutation
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Receptors, Cytokine